Inflammatory and interferon gene expression signatures in patients with mitochondrial disease.

BACKGROUND: People with mitochondrial disease (MtD) are susceptible to metabolic decompensation and neurological symptom progression in response to an infection. Increasing evidence suggests that mitochondrial dysfunction may cause chronic inflammation, which may promote hyper-responsiveness to pathogens and neurodegeneration. We sought to examine transcriptional changes between MtD patients and healthy controls to identify common gene signatures of immune dysregulation in MtD. METHODS: We collected whole blood from a cohort of MtD patients and healthy controls and performed RNAseq to examine transcriptomic differences. We performed GSEA analyses to compare our findings against existing studies to identify commonly dysregulated pathways. RESULTS: Gene sets involved in inflammatory signaling, including type I interferons, interleukin-1ß and antiviral responses, are enriched in MtD patients compared to controls. Monocyte and dendritic cell gene clusters are also enriched in MtD patients, while T cell and B cell gene sets are negatively enriched. The enrichment of antiviral response corresponds with an independent set of MELAS patients, and two mouse models of mtDNA dysfunction. CONCLUSIONS: Through the convergence of our results, we demonstrate translational evidence of systemic peripheral inflammation arising from MtD, predominantly through antiviral response gene sets. This provides key evidence linking mitochondrial dysfunction to inflammation, which may contribute to the pathogenesis of primary MtD and other chronic inflammatory disorders associated with mitochondrial dysfunction.

Locating and testing the healthy context paradox: examples from the INCLUSIVE trial.

BACKGROUND: The healthy context paradox, originally described with respect to school-level bullying interventions, refers to the generation of differences in mental wellbeing amongst those who continue to experience bullying even after interventions successfully reduce victimisation. Using data from the INCLUSIVE trial of restorative practice in schools, we relate this paradox to the need to theorise potential harms when developing interventions; formulate the healthy context paradox in a more general form defined by mediational relationships and cluster-level interventions; and propose two statistical models for testing the healthy context paradox informed by multilevel mediation methods, with relevance to structural and individual explanations for this paradox. METHODS: We estimated two multilevel mediation models with bullying victimisation as the mediator and mental wellbeing as the outcome: one with a school-level interaction between intervention assignment and the mediator; and one with a random slope component for the student-level mediator-outcome relationship predicted by school-level assignment. We relate each of these models to contextual or individual-level explanations for the healthy context paradox. RESULTS: Neither model suggested that the INCLUSIVE trial represented an example of the healthy context paradox. However, each model has different interpretations which relate to a multilevel understanding of the healthy context paradox. CONCLUSIONS: Greater exploration of intervention harms, especially when those accrue to population subgroups, is an essential step in better understanding how interventions work and for whom. Our proposed tests for the presence of a healthy context paradox provide the analytic tools to better understand how to support development and implementation of interventions that work for all groups in a population. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN10751359 .

Predicting neurocognitive function in pediatric brain tumor early survivorship: The neurological predictor scale and the incremental validity of tumor size.

BACKGROUND: The Neurological Predictor Scale (NPS) quantifies cumulative exposure to conventional treatment-related neurological risks but does not capture potential risks posed by tumors themselves. This study evaluated the predictive validity of the NPS, and the incremental value of tumor location and size, for neurocognitive outcomes in early survivorship following contemporary therapies for pediatric brain tumors. PROCEDURE: Survivors (N = 69) diagnosed from 2010 to 2016 were administered age-appropriate versions of the Wechsler Intelligence Scales. Hierarchical multiple regressions examined the predictive and incremental validity of NPS score, tumor location, and tumor size. RESULTS: Participants (51% female) aged 6-20 years (M = 13.22, SD = 4.09) completed neurocognitive evaluations 5.16 years (SD = 1.29) postdiagnosis. The NPS significantly predicted Full-Scale Intelligence Quotient (FSIQ; ΔR2  = .079), Verbal Comprehension Index (VCI; ΔR2  = 0.051), Perceptual Reasoning Index (PRI; ΔR2  = 0.065), and Processing Speed Index (PSI; ΔR2  = 0.049) performance after controlling for sex, age at diagnosis, and maternal education. Tumor size alone accounted for a significant amount of unique variance in FSIQ (ΔR2  = 0.065), PRI (ΔR2  = 0.076), and PSI (ΔR2  = 0.080), beyond that captured by the NPS and relevant covariates. Within the full model, the NPS remained a significant independent predictor of FSIQ (ß = -0.249, P = 0.016), VCI (ß = -0.223, P = 0.048), and PRI (ß = -0.229, P = 0.037). CONCLUSIONS: Tumor size emerged as an independent predictor of neurocognitive functioning and added incrementally to the predictive utility of the NPS. Pretreatment disease burden may provide one of the earliest markers of neurocognitive risk following contemporary treatments. With perpetual treatment advances, measures quantifying treatment-related risk may need to be updated and revalidated to maintain their clinical utility.

Cognitive predictors of social adjustment in pediatric brain tumor survivors treated with photon versus proton radiation therapy.

BACKGROUND: Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. PROCEDURE: Survivors who underwent PRT (n = 38) or XRT (n = 20) participated in a neurocognitive evaluation >1 year post radiotherapy. Group differences in cognitive and social functioning were assessed using analysis of covariance (ANCOVA). Regression analyses examined predictors of peer relations and social skills. RESULTS: Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p > .05). XRT participants were younger at diagnosis (XRT M = 5.0 years, PRT M = 7.6 years) and further out from radiotherapy (XRT M = 8.7 years, PRT M = 4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p = .01) and verbal memory (p < .01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation; χ2 (1) = 38.67, p < .001; χ2 (1) = 5.63, p < .05. Household poverty predicted peer relation difficulties (t = 2.18, p < .05), and verbal memory approached significance (t = -1.99, p = .05). Tumor diameter predicted social skills (t = -2.07, p < .05). CONCLUSIONS: Regardless of radiation modality, survivors are at risk for social challenges. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship, as well as consideration of sociodemographic risk factors.

The "Cinderella sector": The challenges of promoting food and nutrition for young children in early years' settings in England.

The quality of food that children eat in early childhood has profound impacts on their future wellbeing. In England, many children eat the majority of meals in early years' settings including nurseries and childminders. We conducted 16 interviews with 18 stakeholders exploring food provision, the use of voluntary nutrition guidelines, and the effects of government support on the early years' sector. Key themes emerging from our thematic analysis included feeling insufficiently consulted, undervalued, support being unequally distributed, needing to fill multiple support roles for families, disagreement about the role and effect of voluntary nutrition standards, and being chronically underfunded.

Cost-Utility Analysis of a Complex Intervention to Reduce School-Based Bullying and Aggression: An Analysis of the Inclusive RCT.

OBJECTIVES: Bullying and aggression among children and young people are key public mental health priorities. In this study, we evaluated the cost-effectiveness of a complex school-based intervention to address these outcomes within a large-cluster randomized trial (Inclusive). METHODS: Forty state secondary schools were randomly allocated (1:1) to receive the intervention or continue with current practice as controls. Data were collected using paper questionnaires completed in classrooms including measures of their health-related quality of life using the Childhood Utility Index and police and National Health Service resource use. Further detailed data were collected on the cost of delivering the intervention. We calculated incremental cost-effectiveness ratios following the intention-to-treat principle using multilevel linear regression models that allowed for clustering of pupils at the school level. RESULTS: Overall, we found that the intervention was highly cost-effective, with cost-per quality-adjusted life year thresholds of £13 284 and £1875 at 2 years and 3 years, respectively. Analysis of uncertainty in the result at 2 years revealed a 65% chance of being cost-effective, but after 3 years there was a 90% chance that it was cost-effective. CONCLUSION: This study provides strong evidence collected prospectively from a randomized study that this school-based intervention is highly cost-effective. Education- and health-sector policy makers should consider investment in scaling up this intervention.

Treatment age and neurocognitive outcomes following proton beam radiotherapy for pediatric low- and intermediate-grade gliomas.

The relationship between age and neurocognitive functioning following proton beam radiotherapy (PRT) in low- and intermediate-grade gliomas (LIGG) has yet to be examined. Eighteen LIGG patients treated with PRT were prospectively enrolled and received annual neurocognitive evaluations of perceptual/verbal reasoning, working memory, and processing speed postradiotherapy. The median age at diagnosis was 8.2 years (range 1.0-14.7) and the median age at PRT was 9.9 years (range 4.2-17.0). Patients' neurocognitive performance did not change on any measure following PRT (p ≥ .142). We did not observe significant changes in cognitive function over time among a small group of LIGG patients treated with PRT.

Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy.

BACKGROUND: Proton radiotherapy (PRT) may be associated with less neurocognitive risk than photon RT (XRT) for pediatric brain tumor survivors. We compared neurocognitive and academic outcomes in long-term survivors treated with XRT versus PRT. METHODS: Survivors underwent neurocognitive evaluation >1 year after craniospinal (CSI) or focal PRT or XRT. Groups were compared using separate one-way analyses of covariance for the CSI and focal groups. RESULTS: PRT (n = 58) and XRT (n = 30) subgroups were similar on gender (66% male), age at RT (median = 6.5 years), age at follow-up (median = 14.6 years), and government assistance status (32%). PRT and XRT focal groups differed on follow-up interval, shunt history, and total RT dose (all p < .05), whereas PRT and XRT CSI groups differed on follow-up interval, baseline neurocognitive performance score, boost volume, and CSI dose (all p < .05). The PRT focal group outperformed the XRT focal group on inhibition/switching (p = .04). The PRT CSI group outperformed the XRT CSI group on inattention/impulsivity (both p < .05). Several clinical variables (i.e., RT dose, boost field, baseline performance) predicted neurocognitive outcomes (all p < .05). The PRT focal group performed comparably to population means on most neurocognitive measures, while both CSI groups performed below expectation on multiple measures. The XRT CSI group was most impaired. All groups fell below expectation on processing speed, fine motor, and academic fluency (most p < .01). CONCLUSIONS: Findings suggest generally favorable neurocognitive and academic long-term outcomes following focal PRT. Impairment was greatest following CSI regardless of modality. Dosimetry and baseline characteristics are important determinants of outcome alone or in combination with modality.

Engaging parents in digital sexual and reproductive health education: evidence from the JACK trial.

BACKGROUND: Research evidence and international policy highlight the central role that parents play in promoting positive sexual behaviour and outcomes in their children, however they can be difficult to engage in sexual and reproductive health (SRH) education programmes. Digital health promotion that uses online and mobile technologies (OMTs) to promote parent-child communication may offer an innovative solution to reach parents, however, few programmes have used OMTs to involve parents in SRH, and none have reported lessons learned in relation to optimising engagement. This study addresses this gap in the literature by reporting acceptability and feasibility of using OMTs to engage parents in SRH education. Findings will be relevant for those wishing to develop and implement digital SRH programmes with parents internationally. METHODS: The Jack Trial is a UK-wide cluster randomised controlled trial recruiting over 8000 adolescents from 66 socially and religiously diverse post-primary schools. An embedded mixed-methods process evaluation explored user engagement with parent components of the If I Were Jack SRH education programme, which include online animated films and a parent-teen homework exercise. RESULTS: A total of 109 adolescents, teachers, parents and SRH policy experts took part in semi-structured interviews and focus groups, 134 parents responded to an online survey, and 3179 adolescents completed a programme engagement and satisfaction questionnaire. Parents who accessed the materials were positive about them; 87% rated them as 'good or excellent' and 67% said they helped them have conversations with their child about SRH. Web analytics revealed that 27% of contacted parents accessed the digital materials, with 9% viewing the animated films. Only 38% of teachers implemented the homework exercise, mainly because they assumed that students would not complete it or it might result in backlash from parents. CONCLUSIONS: While digital parental materials show promise for engaging parents in SRH education, this study suggests that in order to optimise engagement, parental components that give parents the necessary skills to have conversations with their children about sex should be coupled with efforts to increase school and teacher confidence to communicate with parents on sensitive topics. TRIAL REGISTRATION: ISRCTN99459996 .

Effects of the Learning Together intervention on bullying and aggression in English secondary schools (INCLUSIVE): a cluster randomised controlled trial.

BACKGROUND: Bullying, aggression, and violence among children and young people are some of the most consequential public mental health problems. We tested the Learning Together intervention, which involved students in efforts to modify their school environment using restorative practice and by developing social and emotional skills. METHODS: We did a cluster randomised trial, with economic and process evaluations, of the Learning Together intervention compared with standard practice (controls) over 3 years in secondary schools in south-east England. Learning Together consisted of staff training in restorative practice; convening and facilitating a school action group; and a student social and emotional skills curriculum. Primary outcomes were self-reported experience of bullying victimisation (Gatehouse Bullying Scale; GBS) and perpetration of aggression (Edinburgh Study of Youth Transitions and Crime (ESYTC) school misbehaviour subscale) measured at 36 months. We analysed data using intention-to-treat longitudinal mixed-effects models. This trial was registered with the ISRCTN registry (10751359). FINDINGS: We included 40 schools (20 in each group); no schools withdrew. 6667 (93·6%) of 7121 students participated at baseline and 5960 (83·3%) of 7154 at 36 months. Mean GBS bullying score at 36 months was 0·34 (SE 0·02) in the control group versus 0·29 (SE 0·02) in the intervention group, with a significant adjusted mean difference (-0·03, 95% CI -0·06 to -0·001; adjusted effect size -0·08). Mean ESYTC score at 36 months was 4·33 (SE 0·20) in the control group versus 4·04 (0·21) in the intervention group, with no evidence of a difference between groups (adjusted difference -0·13, 95% CI -0·43 to 0·18; adjusted effect size -0·03). Costs were an additional £58 per pupil in intervention schools than in control schools. INTERPRETATION: Learning Together had small but significant effects on bullying, which could be important for public health, but no effect on aggression. Interventions to promote student health by modifying the whole-school environment are likely to be one of the most feasible and efficient ways of addressing closely related risk and health outcomes in children and young people. FUNDING: National Institute for Health Research, Educational Endowment Foundation.

Longitudinal MRI findings in patient with SLC25A12 pathogenic variants inform disease progression and classification.

Aspartate-glutamate carrier 1 (AGC1) is one of two exchangers within the malate-aspartate shuttle. AGC1 is encoded by the SLC25A12 gene. Three patients with pathogenic variants in SLC25A12 have been reported in the literature. These patients were clinically characterized by neurodevelopmental delay, epilepsy, hypotonia, cerebral atrophy, and hypomyelination; however, there has been discussion in the literature as to whether this hypomyelination is primary or secondary to a neuronal defect. Here we report a 12-year-old patient with variants in SLC25A12 and magnetic resonance imaging (MRI) at multiple ages. Novel compound heterozygous, recessive variants in SLC25A12 were identified: c.1295C>T (p.A432V) and c.1447-2_1447-1delAG. Clinical presentation is characterized by severe intellectual disability, nonambulatory, nonverbal status, hypotonia, epilepsy, spastic quadriplegia, and a happy disposition. The serial neuroimaging findings are notable for cerebral atrophy with white matter involvement, namely, early hypomyelination yet subsequent progression of myelination. The longitudinal MRI findings are most consistent with a leukodystrophy of the leuko-axonopathy category, that is, white matter abnormalities that are most suggestive of mechanisms that result from primary neuronal defects. We present here the first case of a patient with compound heterozygous variants in SLC25A12, including brain MRI findings, in the oldest individual reported to date with this neurogenetic condition.

Pharmacy-Led ß-Lactam Allergy Interview (BLAI) Reduces Duration of Fluoroquinolones Within a Community Hospital.

BACKGROUND: Patients with reported ß-lactam allergies often receive broad-spectrum antimicrobials and have been shown to experience a variety of negative health consequences, such as increased mortality, costs, readmission, and adverse reactions. Current literature focuses on ß-lactam allergy skin testing but lacks evidence on ß-lactam allergy interviews (BLAI) when skin testing is unavailable. OBJECTIVE: This study aimed to test the impact of a pharmacy-led BLAI on duration of fluoroquinolones at a community hospital. METHODS: A quasi-experimental design with a prospective cohort design and historical control group was used to assess patients with reported penicillin (PCN) allergies in a community hospital. The primary outcome was duration of fluoroquinolones before and after implementation of BLAI. Secondary outcomes included length of stay (LOS), percentage of patients switched to a ß-lactam antibiotic, percentage of antimicrobial stewardship recommendations made/accepted, and discrepancies between allergy in medical record and interview-reported allergy. Nonparametric continuous data and medians were evaluated by Mann-Whitney U. RESULTS: A total of 80 patients were included in the study (43 in the control group and 37 in the prospective group). Fluoroquinolone duration was reduced after the implementation of BLAI (3.7 vs 2.7 days, P = 0.027). In all, 49% of patients in the prospective group were switched to a ß-lactam antibiotic after BLAI, with no allergic reactions, adverse effects, or impact on LOS. Conclusion and Relevance: BLAI resulted in a significant reduction in fluoroquinolone duration in patients with PCN allergies and may represent a safe and effective option for institutions lacking skin-testing capabilities.

Evidence on public health interventions in humanitarian crises.

Recognition of the need for evidence-based interventions to help to improve the effectiveness and efficiency of humanitarian responses has been increasing. However, little is known about the breadth and quality of evidence on health interventions in humanitarian crises. We describe the findings of a systematic review with the aim of examining the quantity and quality of evidence on public health interventions in humanitarian crises to identify key research gaps. We identified 345 studies published between 1980 and 2014 that met our inclusion criteria. The quantity of evidence varied substantially by health topic, from communicable diseases (n=131), nutrition (n=77), to non-communicable diseases (n=8), and water, sanitation, and hygiene (n=6). We observed common study design and weaknesses in the methods, which substantially reduced the ability to determine causation and attribution of the interventions. Considering the major increase in health-related humanitarian activities in the past three decades and calls for a stronger evidence base, this paper highlights the limited quantity and quality of health intervention research in humanitarian contexts and supports calls to scale up this research.

Public housing agency preferences for the homeless as a policy lever: Examining county-level housing subsidy receipt and maltreatment rates.

This study examines the relationship between county Public Housing Agency (PHA) practices that prioritize families experiencing homelessness and county-level child maltreatment rates. Using data from a survey of PHAs and the National Child Abuse and Neglect Data System (NCANDS) with a sample of 534 counties, we find that policies which give preference to homeless households for housing assistance are associated with reduced victimization and substantiation rates, while policies that reduce barriers to assistance eligibility are associated with reporting rates. Our findings suggest that beyond prioritizing homeless families for housing assistance as a means of ending homelessness, providing families with more expedient access to a valuable public subsidy may have important positive externalities, such as reduced CPS involvement. Additional partnerships between child welfare agencies and housing providers, particularly those that provide housing subsidies, may be worthy of additional investment and evaluation.

Cognitive and numerosity predictors of mathematical skills in middle school.

There is a strong research base on the underlying concomitants of early developing math skills. Fewer studies have focused on later developing skills. Here, we focused on direct and indirect contributions of cognitive measures (e.g., language, spatial skills, working memory) and numerosity measures, as well as arithmetic proficiency, on key outcomes of fraction performance, proportional reasoning, and broad mathematics achievement at sixth grade (N=162) via path analysis. We expected a hierarchy of skill development, with predominantly indirect effects of cognitive factors via number and arithmetic. Results controlling for age showed that the combination of cognitive, number, and arithmetic variables cumulatively accounted for 38% to 44% of the variance in fractions, proportional reasoning, and broad mathematics. There was consistency across outcomes, with more proximal skills providing direct effects and with the effects of cognitive skills being mediated by number and by more proximal skills. Results support a hierarchical progression from domain-general cognitive processes through numerosity and arithmetic skills to proportional reasoning to broad mathematics achievement.

Focal targeting by human ß-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis.

Virulence factor secretion and assembly occurs at spatially restricted foci in some Gram-positive bacteria. Given the essentiality of the general secretion pathway in bacteria and the contribution of virulence factors to disease progression, the foci that coordinate these processes are attractive antimicrobial targets. In this study, we show in Enterococcus faecalis that SecA and Sortase A, required for the attachment of virulence factors to the cell wall, localize to discrete domains near the septum or nascent septal site as the bacteria proceed through the cell cycle. We also demonstrate that cationic human ß-defensins interact with E. faecalis at discrete septal foci, and this exposure disrupts sites of localized secretion and sorting. Modification of anionic lipids by multiple peptide resistance factor, a protein that confers antimicrobial peptide resistance by electrostatic repulsion, renders E. faecalis more resistant to killing by defensins and less susceptible to focal targeting by the cationic antimicrobial peptides. These data suggest a paradigm in which focal targeting by antimicrobial peptides is linked to their killing efficiency and to disruption of virulence factor assembly.

Decision-making criteria among European patients: exploring patient preferences for primary care services.

BACKGROUND: Health economics preference-based techniques, such as discrete choice experiments (DCEs), are often used to inform public health policy on patients' priorities when choosing health care. Although there is general evidence about patients' satisfaction with general-practice (GP) care in Europe, to our knowledge no comparisons are available that measure patients' preferences in different European countries, and use patients' priorities to propose policy changes. METHODS: A DCE was designed and used to capture patients' preferences for GP care in Germany, England and Slovenia. In the three countries, 841 eligible patients were identified across nine GP practices. The DCE questions compared multiple health-care practices (including their 'current GP practice'), described by the following attributes: 'information' received from the GP, 'booking time', 'waiting time' in the GP practice, 'listened to', as well as being able to receive the 'best care' available for their condition. Results were compared across countries looking at the attributes' importance and rankings, patients' willingness-to-wait for unit changes to the attributes' levels and changes in policy. RESULTS: A total of 692 respondents (75% response rate) returned questionnaires suitable for analysis. In England and Slovenia, patients were satisfied with their 'current practice', but they valued changes to alternative practices. All attributes influenced decision-making, and 'best care' or 'information' were more valued than others. In Germany, almost all respondents constantly preferred their 'current practice', and other factors did not change their preference. CONCLUSION: European patients have strong preference for their 'status quo', but alternative GP practices could compensate for it and offer more valued care.

An Empty Scoping Review of Emergency Department to School Transition for Youth with Mental Health Concerns.

The number of youth Emergency Department (ED) visits due to mental health concerns has been steadily increasing with a large number of youth being referred from school. Despite the increase in ED visits, there has not been an increase in the number of students who are actually admitted to the hospital. Further, youth referred from school are more likely to be discharged from the ED. Given the unique relationship between school and ED referrals and the large number of youth who do not require hospitalization, this study sought to understand how schools are supporting students who return to school after an ED visit. We conducted a scoping review to identify programs and practices to support ED to school transition. Two reviewers screened 907 manuscripts, but none of the manuscripts met the inclusion criteria. We discuss the importance of supporting students returning to school from the ED and draw from the literature on hospital to school transition to make recommendations for educators.

mHealth interventions for postpartum family planning in LMICs: A realist review.

The unmet need for family planning is a pervasive public health concern in many low- and middle-income countries (LMICs). Mobile health (mHealth) interventions have been designed and implemented in LMIC settings to address this issue through health information dissemination via voice calls, apps, and short message services (SMS). Although the impact of mHealth programmes on postpartum family planning outcomes have been systematically reviewed, the contexts, conditions, and mechanisms underpinning programme engagement and their impact on outcomes remain unclear. This study aims to formulate hypotheses in the form of context-mechanism-outcome configurations (CMOCs) of whether, how, why, for whom, and in what contexts mHealth interventions implemented in LMICs influence postpartum family planning (PPFP) outcomes. We conducted a realist review of peer-reviewed and grey literature. Peer-reviewed literature was identified through MEDLINE, Embase, Global Health, Web of Science, and Google Scholar. Grey Literature was identified through The National Grey Literature Conference, FHI 360, Guttmacher Institute, Population Council, and MSI Reproductive Choices. Inclusion criteria were updated as the review progressed. Narrative data were analysed using dimensional analysis to build CMOCs. Two overarching concepts (underpinned by 12 CMOCs) emerged from the 37 included records: mobile phone access, use, and ownership as well as women's motivation. Women's confidence to independently own, access, and operate a mobile phone was a central mechanism leading to mHealth programme engagement and subsequent change in PPFP knowledge, awareness, and outcomes. Receiving family and social support positively interacted with this while low digital literacy and harmful gender norms pertaining to prescribed domestic duties and women's household influence were barriers to programme engagement. Intrinsic motivation for health improvement functioned at times both as a context and potential mechanism influencing mHealth programme engagement and PPFP outcomes. However, these contexts rarely occur in isolation and need to be evaluated as co-occurring phenomena. (Review registration: PROSPERO CRD42023386841).

Human Cell-Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature-on-chip Models.

Microphysiological and organ-on-chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs-on-chip have advanced considerably, most platforms rely on animal-derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell-derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor-derived hCDM composite hydrogels could address technical gaps in human organs-on-chip development and serve as substrates to promote vascularization.